rs8112982

Positions:

• chr19-8091324-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000600128.6(FBN3):​c.6031+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,149,846 control chromosomes in the GnomAD database, including 1,446 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.059 (869 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (577 hom.)
• Consequence: FBN3 ENST00000600128.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

Genes affected

FBN3 (HGNC:18794): (fibrillin 3) This gene encodes a memebr of the fibrillin protein family. Fibrillins are extracellular matrix molecules that assemble into microfibrils in many connective tissues. This gene is most highly expressed in fetal tissues and its protein product is localized to extracellular microfibrils of developing skeletal elements, skin, lung, kidney, and skeletal muscle. This gene is potentially involved in Weill-Marchesani syndrome. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.6031+141G>A		intron_variant		ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.6031+141G>A		intron_variant		1	NM_032447.5	ENSP00000470498
FBN3	ENST00000270509.6	c.6031+141G>A		intron_variant		1		ENSP00000270509
FBN3	ENST00000601739.5	c.6031+141G>A		intron_variant		1		ENSP00000472324
FBN3	ENST00000651877.1	c.6157+141G>A		intron_variant				ENSP00000498507	P1

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9025 AN: 152138 Hom.: 864 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0464

GnomAD4 exome AF: 0.00844 AC: 8415 AN: 997590 Hom.: 577 AF XY: 0.00832 AC XY: 4181 AN XY: 502748

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.0000561

Gnomad4 EAS exome AF: 0.0184

Gnomad4 SAS exome AF: 0.0228

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000563

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome AF: 0.0595 AC: 9056 AN: 152256 Hom.: 869 Cov.: 32 AF XY: 0.0582 AC XY: 4335 AN XY: 74470

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0409 Hom.: 93

Bravo AF: 0.0674

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8112982; hg19: chr19-8156208;